DESCRIPTION: The mechanisms by which embryonic cartilages follow alternative pathways and give rise to either permanent cartilages or transient endochondral cartilages are largely unknown. Data from the literature and from the principal investigator's laboratory implicate the TGF-betas as key regulators of chondrocyte development and phenotypic expression during skeletogenesis. Taken together, they support the hypothesis that the TGF-betas have distinct effects and modes of action in permanent and transient chondrocytes. The hypothesis will be tested in three specific aims that will 1) define the isoforms and latency status of the TGF-betas produced by developing permanent and transient chondrocytes, 2) determine the availability of the TGF-betas and mechanisms of activation in chondrocytes at different stages of development, and 3) define the TGF-beta receptor profiles in developing chondrocytes. Collectively, these data will provide important information on the role of the TGF-betas in skeletal development by elucidating the mechanisms by which these growth factors can exert distinct effects on different populations of chondrocytes. Such knowledge will contribute to a better understanding of skeletal defects that may originate from alterations in TGF-beta-dependent pathways.